title: Acute exposure to diesel exhaust impairs nitric oxide-mediated endothelial vasomotor function by increasing endothelial oxidative stress.
abstract: Exposure to diesel exhaust was recently identified as an important cardiovascular risk factor, but whether it impairs nitric oxide (NO)-mediated endothelial function and increases production of reactive oxygen species (ROS) in endothelial cells is not known. We tested these hypotheses in a randomized, controlled, crossover study in healthy male volunteers exposed to ambient and polluted air (n=12). The effects of skin microvascular hyperemic provocative tests, including local heating and iontophoresis of acetylcholine and sodium nitroprusside, were assessed using a laser Doppler imager. Before local heating, skin was pretreated by iontophoresis of either a specific NO-synthase inhibitor (L-N-arginine-methyl-ester) or a saline solution (Control). ROS production was measured by chemiluminescence using the lucigenin technique in human umbilical vein endothelial cells preincubated with serum from 5 of the subjects. Exposure to diesel exhaust reduced acetylcholine-induced vasodilation (P<0.01) but did not affect vasodilation with sodium nitroprusside. Moreover, the acetylcholine/sodium nitroprusside vasodilation ratio decreased from 1.51 ± 0.1 to 1.06 ± 0.07 (P<0.01) and was correlated to inhaled particulate matter 2.5 (r=-0.55; P<0.01). NO-mediated skin thermal vasodilatation decreased from 466 ± 264% to 29 ± 123% (P<0.05). ROS production was increased after polluted air exposure (P<0.01) and was correlated with the total amount of inhaled particulate matter <2.5 μm (PM2.5). In healthy subjects, acute experimental exposure to diesel exhaust impaired NO-mediated endothelial vasomotor function and promoted ROS generation in endothelial cells. Increased PM2.5 inhalation enhances microvascular dysfunction and ROS production.
authors.affiliation: Department of Cardiology, Erasme Hospital, 808 Lennik St, 1070 Brussels, Belgium. Aurelien.Wauters@erasme.ulb.ac.be
authors.forename: Aurélien
authors.initials: A
authors.lastname: Wauters
authors.forename: Céline
authors.initials: C
authors.lastname: Dreyfuss
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Pochet
authors.forename: Patrick
authors.initials: P
authors.lastname: Hendrick
authors.forename: Guy
authors.initials: G
authors.lastname: Berkenboom
authors.forename: Philippe
authors.initials: P
authors.lastname: van de Borne
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Argacha
mesh_terms: D000328:Adult; D000397:Air Pollution / Q000009:adverse effects; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D013481:Superoxides; D009569:Nitric Oxide
keywords: endothelium, vascular; laser-Doppler flowmetry; nitric oxide; reactive oxygen species; vasodilation; vehicle emissions